Motivation to work for amino acids requires acute dopaminergic activity.

Aberrant motivation is a hallmark of many psychiatric disorders, and studying motivation in model systems can be useful to understand the neural mechanisms of these disorders. Having versatile, ethologically relevant assays with which to measure motivation is therefore important. However, motivational assays in Drosophila have not been able to measure willingness to exert effort to consume food. Here, we took advantage of the fact that flies prefer to feed on liquid over solid foods to develop a new assay using agarose as a barrier to feeding, which we termed the Fly Liquid vs Agarose Motivation Evaluation (FLAME). Unlike motivational assays based on overcoming bitterness, the FLAME measures willingness to work and is less confounded by deprivation acting on peripheral sensing of the modality to overcome. By depriving flies of specific nutrients and measuring their choice to overcome semi-solid agarose food to get those nutrients, we show that the FLAME is a versatile assay for measuring motivation. We show that flies choose to overcome agarose to consume sugar, salt, or amino acids, depending on the specific of prior deprivation. We then show that show that flies rely on acute activity in a subset of their dopamine neurons during the choice period in order to work for amino acids when deprived. The FLAME thus allows the investigation of specific neural mechanisms of motivation.